Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

ACTIN AND ACTIN-BINDING PROTEINS
913
(A)
filamin
dimer
50 nm
Figure 16–24 Filamin cross-links actin
filaments into a three-dimensional
network and is required for normal
neuronal migration. (A) Each filamin
homodimer is about 160 nm long when
fully extended and forms a flexible, highangle
link between two adjacent actin
filaments. A set of actin filaments crosslinked
by filamin forms a mechanically
strong web or gel. (B) Magnetic resonance
imaging of a normal human brain (left)
and of a patient with periventricular
heterotopia (right) caused by mutation
in the filamin A gene. In contrast to the
smooth ventricular surface in the normal
brain, a rough zone of cortical neurons
(arrowheads) is seen along the lateral walls
of the ventricles, representing neurons
that have failed to migrate to the cortex
during brain development. Remarkably,
although many neurons are not in the
right place, the intelligence of affected
individuals is frequently normal or only
mildly compromised, and the major clinical
syndrome is epilepsy that often starts in the
second decade of life. (B, adapted from
Y. Feng and C.A. Walsh, Nat. Cell Biol.
6:1034–1038, 2004. With permission
from Macmillan Publishers Ltd.)
(B)
in promoting mechanical stability is the long, thin axon of neurons in the nematode
worm Caenorhabditis elegans, where spectrin is required to keep them from
MBoC6 m16.51/16.24
breaking during the twisting motions the worms make during crawling.
The connections of the cortical actin cytoskeleton to the plasma membrane
are only partially understood. Members of the ERM family (named for its first
three members, ezrin, radixin, and moesin), help organize membrane domains
through their ability to interact with transmembrane proteins and the underlying
cytoskeleton. In so doing, they not only provide structural links to strengthen the
cell cortex, but also regulate the activities of signal transduction pathways. Moesin
also increases cortical stiffness to promote cell rounding during mitosis. Measurements
by atomic force microscopy indicate that the cell cortex remains soft during
mitosis when moesin is depleted. ERM proteins are thought to bind to and organize
the cortical actin cytoskeleton in a variety of contexts, thereby affecting the
shape and stiffness of the membrane as well as the localization and activity of
signaling molecules.
Bacteria Can Hijack the Host Actin Cytoskeleton
The importance of accessory proteins in actin-based motility and force production
is illustrated beautifully by studies of certain bacteria and viruses that use
components of the host-cell actin cytoskeleton to move through the cytoplasm.
The cytoplasm of mammalian cells is extremely viscous, containing organelles
and cytoskeletal elements that inhibit diffusion of large particles like bacteria or
viruses. To move around in a cell and invade neighboring cells, several pathogens,
including Listeria monocytogenes (which causes a rare but serious form of
food poisoning), overcome this problem by recruiting and activating the Arp 2/3
complex at their surface. The Arp 2/3 complex nucleates the assembly of actin
filaments that generate a substantial force and push the bacterium through the